Interest in molybdenum- and tungsten-catalyzed reactions of allyl substrates with nucleophiles has been promoted by the regioselectivity shown by these complexes, as compared to that of palladium complexes. See, for example, for molybdenum, Trost and Merlic, 1990, Rubio and Liebeskind, 1993, Trost and Hachiya, 1998; and for tungsten, Trost and Hung, 1983, and Trost et al., 1987. Palladium catalyzed reactions generally provide products from attack at the less substituted terminus. This regiochemistry (shown at eq 1, path a in FIG. 1) is particularly favored for alkylation of aryl-substituted allyl systems, even with catalysts having chiral ligands (Godleski, 1991). Molybdenum and tungsten catalysts, on the other hand, generally favor attack at the more substituted terminus (eq 1, path b). Complexes of these metals are also less costly than palladium catalysts.
Such alkylations have shown limitations, however. For example, molybdenum-catalyzed alkylations of cinnamyl substrates, using dimethyl malonate, have been shown to favor attack at the less substituted allyl terminus (Trost and Lautens, 1982, 1987; Trost and Merlic, 1990). In general, there have been no reports, prior to the studies described herein, of molybdenum-catalyzed alkylations showing both high regio- and enantioselectivity. Early studies utilizing a variety of chiral nitrogen based ligands for molybdenum failed to give any appreciable asymmetric induction (Merlic, 1988). A study utilizing tungsten catalysts with chiral phosphino-oxazoline ligands reported that the isostructural molybdenum complex was “not useful as a catalyst” (Lloyd-Jones & Pflatz, 1995).
Products of the type shown in reaction path (b), having high optical purity, would find great value as building blocks in the synthesis of biologically useful compounds. A low-cost, versatile, stereoselective catalytic route to such compounds would thus be desirable.